Histologic Classifier of Radiosensitivity to Spine Stereotactic Body Radiation Therapy

Spine stereotactic body radiation therapy (SBRT) outperforms conventional radiation therapy in preventing local failure (LF). Data comparing dose-fractionation schemes on the likelihood of LF and vertebral compression fracture (VCF) are limited.

This is a retrospective cohort study of 1838 patients (2702 lesions) treated between 2014 and 2023 at a single institution with de novo spine SBRT. LF was defined as progressive disease on magnetic resonance imaging. VCF was defined as progressive or new fracture on magnetic resonance imaging without LF. Death was considered a competing risk.

Median follow-up after SBRT for surviving patients was 25 months (IQR 13-43 months). Eleven hundred ninety-seven lesions (44%) received 27 Gy in 3 fractions, 931 (34%) received 30 Gy in 3 fractions, and 574 lesions (21%) received 24 Gy in 1 fraction. Three hundred nine treatment courses involved separation surgery (11%), and 311 lesions (11%) were epidural spinal cord compression score 2 to 3. For lesions treated with 24 Gy in 1 fraction, 30 Gy in 3 fractions, and 27 Gy in 3 fractions, 2-year LF rates (95% CI) were 7% (5%-9%), 11% (9%-13%), and 17% (15%-20%), respectively (P < .001). Two-year VCF rates (95% CI) requiring stabilization were 10% (8%-13%; 24 Gy in 1 fraction), 2% (1%-3%; 27 Gy in 3 fractions), and 3% (2%-5%; 30 Gy in 3 fractions) (P < .001). For the 3-fraction regimens specifically, 30 Gy was associated with a higher overall VCF rate (P = .022) and lower LF rate (P < .001), but there was no significant difference in the risk of VCF requiring intervention (P = .15). Univariable and multivariable regression revealed histologic-based differences in LF: 2-year LF rates were 8.6% (95% CI, 6.4%-11%) for class A lesions (prostate and breast cancers), 26% (95% CI, 20%-32%) for class C lesions (cholangio-, hepatocellular, and colorectal carcinoma), and 13% (95% CI, 12%-15%) for class B lesions (other histologies) (P < .001). For class B to C, epidural spinal cord compression 2 to 3 lesions (n = 261), surgery plus SBRT reduced LF compared to SBRT alone (7.9 vs 20% at 2 years, P = .051), though this did not reach statistical significance.

The preferred hypofractionated SBRT regimen-even for class A histologies-is 30 Gy in 3 fractions, offering superior local control with similar risk of VCF requiring intervention, compared to 27 Gy. For class B to C lesions with high-grade epidural disease, separation surgery prior to SBRT may improve local control.